Our Center is studying the biochemical and physiologic pathways responsible for the inflammation associated with urticaria, angioedema, urticarial vasculitis and vasculitis associated with autoimmune diseases. We know that cold urticaria is histamine-mediated, and, in some cases IgE-dependent. We hope to determine the mechanism by which IgE leads to mast cell degranulation in this disorder as well as dermatographism and assess the role of acetylcholine release in the pathogenesis of cholinergic urticaria. A possible role for kinins and arachidonic acid metabolites as mediators of cholinergic urticaria will be sought and the role of kinins in causing the swelling seen in hereditary angioedema will be defined. A link between the Hageman factor-kallikrein system and the classical complement cascade will be sought in whole plasma and further studied using purified proteins. We will also examine possible immune and non-immune mechanims responsible for the release of histamine and other vasoactive agents in chronic urticaria and angioedema. Finally, we will examine mechanisms by which inflammation may be modulated in connective tissue diseases and other vasculitides including identification of antigens responsible for immune complex formation, the role of vasoactive factors in immune complex localization and the relationship of disease severity and reticuloendothelial clearance of complexes.